Single-cell transcriptome and crosstalk analysis reveals immune alterations and key pathways in the bone marrow of knee OA patients.

Autor:	Chatterjee P; Marcus Center for Therapeutic Cell Characterization and Manufacturing, The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA.; The Parker H. Petit Institute for Bioengineering and Biosciences Georgia Institute of Technology, Atlanta, GA, USA., Stevens HY; Marcus Center for Therapeutic Cell Characterization and Manufacturing, The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA.; The Parker H. Petit Institute for Bioengineering and Biosciences Georgia Institute of Technology, Atlanta, GA, USA., Kippner LE; Marcus Center for Therapeutic Cell Characterization and Manufacturing, The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA.; The Parker H. Petit Institute for Bioengineering and Biosciences Georgia Institute of Technology, Atlanta, GA, USA., Bowles-Welch AC; Marcus Center for Therapeutic Cell Characterization and Manufacturing, The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA.; The Parker H. Petit Institute for Bioengineering and Biosciences Georgia Institute of Technology, Atlanta, GA, USA., Drissi H; Department of Orthopaedics, Emory University School of Medicine, Atlanta, GA 30322, USA., Mautner K; Department of Orthopaedics, Emory University School of Medicine, Atlanta, GA 30322, USA., Yeago C; The Parker H. Petit Institute for Bioengineering and Biosciences Georgia Institute of Technology, Atlanta, GA, USA., Gibson G; School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA., Roy K; Marcus Center for Therapeutic Cell Characterization and Manufacturing, The Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA.; Department of Biomedical Engineering, School of Engineering, Vanderbilt University, Nashville, TN, USA.; Department of Pathology, Microbiology and Immunology, School of Medicine, Vanderbilt University, Nashville, TN, USA.; Department of Chemical and Biomolecular Engineering, School of Engineering, Vanderbilt University, Nashville, TN, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2024 Aug 26; Vol. 27 (9), pp. 110827. Date of Electronic Publication: 2024 Aug 26 (Print Publication: 2024).
DOI:	10.1016/j.isci.2024.110827
Abstrakt:	Knee osteoarthritis (OA) is a significant medical and economic burden. To understand systemic immune effects, we performed deep exploration of bone marrow aspirate concentrates (BMACs) from knee-OA patients via single-cell RNA sequencing and proteomic analyses from a randomized clinical trial (MILES: NCT03818737). We found significant cellular and immune alterations in the bone marrow, specifically in MSCs, T cells and NK cells, along with changes in intra-tissue cellular crosstalk during OA progression. Unlike previous studies focusing on injury sites or peripheral blood, our probe into the bone marrow-an inflammation and immune regulation hub-highlights remote organ impact of OA, identifying cell types and pathways for potential therapeutic targeting. Our findings highlight increased cellular senescence and inflammatory pathways, revealing key upstream genes, transcription factors, and ligands. Additionally, we identified significant enrichment in key biological pathways like PI3-AKT-mTOR signaling and IFN responses, showing their potentially crucial role in OA onset and progression. Competing Interests: The authors declare no competing interests. (© 2024 The Author(s).)
Databáze:	MEDLINE
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